Haarsma Joost, Harmer Catherine J, Tamm Sandra
Wellcome Centre for Human Neuroimaging, University College London, London, UK.
Department of Psychiatry and Oxford Health NHS Foundation Trust, Warneford Hospital, University of Oxford, Oxford, UK.
Brain Neurosci Adv. 2021 May 3;5:23982128211007772. doi: 10.1177/23982128211007772. eCollection 2021 Jan-Dec.
Ketamine, classical psychedelics and sleep deprivation are associated with rapid effects on depression. Interestingly, these interventions also have common psychotomimetic actions, mirroring aspects of psychosis such as an altered sense of self, perceptual distortions and distorted thinking. This raises the question whether these interventions might be acute antidepressants through the same mechanisms that underlie some of their psychotomimetic effects. That is, perhaps some symptoms of depression can be understood as occupying the opposite end of a spectrum where elements of psychosis can be found on the other side. This review aims at reviewing the evidence underlying a proposed , suggesting that a range of psychotomimetic interventions are also acute antidepressants as well as trying to explain these common features in a hierarchical predictive coding framework, where we hypothesise that these interventions share a common mechanism by increasing the flexibility of prior expectations. Neurobiological mechanisms at play and the role of different neuromodulatory systems affected by these interventions and their role in controlling the precision of prior expectations and new sensory evidence will be reviewed. The proposed hypothesis will also be discussed in relation to other existing theories of antidepressants. We also suggest a number of novel experiments to test the hypothesis and highlight research areas that could provide further insights, in the hope to better understand the acute antidepressant properties of these interventions.
氯胺酮、经典致幻剂和睡眠剥夺与对抑郁症的快速疗效相关。有趣的是，这些干预措施也具有共同的拟精神病作用，反映出精神病的一些方面，如自我感觉改变、感知扭曲和思维紊乱。这就提出了一个问题，即这些干预措施是否可能通过其某些拟精神病作用背后的相同机制成为急性抗抑郁药。也就是说，也许抑郁症的某些症状可以被理解为处于一个光谱的另一端，而精神病的元素则在另一端。本综述旨在回顾一项提议背后的证据，该提议认为一系列拟精神病干预措施也是急性抗抑郁药，并试图在分层预测编码框架中解释这些共同特征，我们假设这些干预措施通过增加先验期望的灵活性而共享一种共同机制。将回顾其中起作用的神经生物学机制以及受这些干预措施影响的不同神经调节系统的作用，以及它们在控制先验期望和新感官证据的精确性方面的作用。还将结合其他现有的抗抑郁药理论来讨论所提出的假设。我们还提出了一些新颖的实验来检验该假设，并突出那些可以提供进一步见解的研究领域，以期更好地理解这些干预措施的急性抗抑郁特性。
